29 October 2019

The "anxiety gene"

Anxiety disorders in mice will help treat mental disorders in humans

"First-hand science"

Scientists from the University of Utah (USA) have found an "anxiety gene" in mice, when it is "turned off", a neurological disorder begins in animals, similar in symptoms to an anxiety disorder in humans. Many people, especially women, face this mental pathology during their lives. But the causes and mechanisms of the development of these disorders are still not really understood.

In the modern world, the number of people suffering from depressive and anxiety disorders is constantly growing. This group of mental disorders also includes post-traumatic stress disorder, the cause of which may be not only stress experienced during military operations ("Vietnam syndrome", "Afghan syndrome"), but also sexual violence, childhood abuse, terrorist acts, natural and man-made disasters, long-term illnesses and the death of loved ones, even financial difficulties... All anxiety disorders have their own set of symptoms, which are grouped around a common core – irrational fear.

To learn how to detect people from risk groups, diagnose these diseases and effectively treat them, it is necessary to understand their causes and mechanisms. For example, not so long ago it was believed that increased anxiety is one of the manifestations of depression. However, today it has been established that, although these diseases do not exclude each other, the mechanisms of their formation are fundamentally different.

Both environmental factors and genetic features play an important role in the development of anxiety disorders. Thus, genotypes with a high risk of developing this pathology have been identified. However, the interrelationships of a certain genotype and the peculiarities of human adaptation to a certain socio-cultural environment are quite confusing and often not obvious.

Scientists from the University of Utah (USA) have found – so far only in mice – an "anxiety gene", when "turned off" which animals showed fairly clear symptoms of a neurological disorder similar to human symptoms. This discovery was made several years ago in the study of microglia – "servicing" brain cells that protect neurons from various infections and damage, as well as remove decay products. These cells are formed in the bone marrow and are actually cells of the immune system.

It turned out that the Hoxb8 protein is actively synthesized in microglial cells of one of the types. Having "turned off" the corresponding gene in the brain of mice, scientists were surprised to find that mice began to devote so much time to grooming that they gradually began to go bald. This behavior was very similar to trichotillomania (obsessive pulling of one's own hair) in people with obsessive-compulsive disorder. This behavior was most pronounced in females, who, unlike males, also demonstrated other behavioral and physiological aspects of anxiety disorder. In standard stress tests, females showed elevated levels of the stress hormone cortisol and a distinct pupil dilation reaction.

It has recently been found that intersex differences in the level of anxiety in mice are determined by sex hormones. It has been observed that females with the Hoxb8 gene turned off begin to engage in their fur more actively with the onset of puberty. The relationship between female sex hormones was confirmed experimentally in females whose synthesis of female sex hormones was blocked, and males who were injected with these hormones.

Article by Tränkner et al. A Microglia Sublineage Protects from Sex-Linked Anxiety Symptoms and Obsessive Compulsion is published in the journal Cell Reports.

The anxious behavior and excessive stress responses in mice with Hoxb8 "turned off" strongly resemble the symptoms of an anxiety disorder in humans, so these mice can be used as a biological model for research purposes and, ultimately, for testing potential drugs.

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